TABLE 2.

Comparison of the large intervention studies VIOLET and VITDALIZE—two studies that at first glance appear similar, but nevertheless have significant differences, regarding drug administration, inclusion criteria, and primary endpoints.

	VIOLET (NCT03096314)	VITDALIZE (NCT03188796)
Inclusion criteria	Vitamin D level ≤ 20 ng/ml	25(OH)D ≤ 12 ng/ml
Number of cases	Planned 3,000, aborted after 1,360 at first interim analysis due to “futility.” Analyzed 1,078	Planned 2,400, an interim analysis As of October 2022: 900 patients included
Population	Patients at risk for ARDS	ICU-patients
Bolus output	A single bolus of 540,000 IU	Bolus administration of 540,000 IU and additional daily administrations of 4,000 IU over a 90-day period (corresponding to a total vitamin D administration of 900,000 IU over a 90-day period).
Primary endpoint	90-day mortality	All-cause mortality after 28 days

In the VIOLET study, 1,360 patients were screened and found to have vitamin D levels of <20 ng/ml using point of care testing, but only 1,078 who actually had a vitamin D level <20 ng/ml in subsequent LC/MS testing were analyzed. However, in the previous VITDAL-ICU study, only the subgroup with levels <12 ng/ml showed significantly reduced 28-day mortality, not the subgroup with vitamin D between 12 and 20 ng/ml (34). Based on these results, the design of the VITDALIZE study was planned and created (correct subgroup, correct endpoint). Mention should also be made of the VITDALIZE-Kids study (NCT03742505), led by JD McNally in Canada, which has included critically ill children since 2019 (planned 766, as of October 2022: >200; primary endpoint: health related quality of life).